Both exceeded the 2- to 3-point difference considered clinically meaningful on the Hamilton Rating Scale for Depression (HAM-D) used to measure this primary endpoint in the Study of Antidepressants in Parkinson's Disease (SAD-PD).

Unlike the older tricyclic antidepressants -- which have cardiac, autonomic, and anticholinergic side effects in Parkinson's patients -- both drugs tested in the trial were well tolerated without any impact on motor function.

A prior study done in Parkinson's disease suggested that the older tricyclics might be preferred despite adverse effects and questioned the efficacy of selective serotonin reuptake inhibitors after it uncovered no improvement in depression with paroxetine beyond that with placebo.

The conflicting results may have stemmed from the shorter duration of treatment, higher dropout rate, and strategy used for missing data in that study, Richard's group suggested.

The treatment effects with paroxetine and extended release venlafaxine were convincing and robust, according to an editorial by Joseph H. Friedman, MD, of Butler Hospital in Providence, R.I., and Daniel Weintraub, MD, of the University of Pennsylvania in Philadelphia.

"Most importantly, this study provides level I evidence for an antidepressant treatment effect in patients without dementia with very mild Parkinson's disease," they wrote.

The editorialists cautioned, though, that it's not clear whether the SAD-PD results would generalize to more severely affected Parkinson's patients. The number needed to treat to achieve depression remission was 13 with paroxetine and 24 with venlafaxine because of the high placebo response, they added.

The multicenter trial randomized 115 Parkinson's disease patients without dementia to 12 weeks of treatment with paroxetine or the serotonin and norepinephrine reuptake inhibitor venlafaxine XR at maximum daily doses of 40 mg and 225 mg, respectively, or placebo.

All three groups showed improvements by week 12, with mean reductions in HAM-D scores of 13.0 with paroxetine, 11.0 with extended release venlafaxine, and 6.8 with placebo.

While both active treatments were superior to placebo, the two didn't differ from each other (P=0.28).

But the proportion meeting remission criteria by reaching a HAM-D score of 7 points or less at week 12 did not differ significantly among the groups at 44% with paroxetine, 37% with extended release venlafaxine, and 32% with placebo.

Likewise, the percentage with a response of at least a 50% reduction in HAM-D score at week 12 didn't differ significantly among groups, at 68%, 53%, and 44%, respectively.

The lack of statistical significance on that outcome may have been because of the substantially lower than planned sample size, the researchers suggested.

Total and motor scores on the Unified Parkinson's Disease Rating Scale improved across groups without differences or treatment-related worsening of motor function. Quality of life wasn't affected overall by either antidepressant.

The researchers cautioned that while the two antidepressants appeared similar in effects in the trial, it wasn't powered to make comparisons between the two.

Nor was the trial large enough to look for characteristics of responders.

"Further research aimed at understanding predictors of response, including identification of patients who may respond preferentially to one class of medication versus another, is warranted," Richard's group wrote.

The study was supported by grant funds from the National Institute of Neurological Disorders and Stroke and the General Clinical Research Center at Johns Hopkins University School of Medicine.

Richard reported serving on a scientific advisory board for the Michael J. Fox Foundation; receiving a speaker honorarium from Teva Pharmaceutical; and receiving research support from Neurologix, Eli Lilly, the NIH/NINDS, Cornell University, and the Michael J. Fox Foundation.

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